Cassava Sciences Announces Phase 2a Study of PTI-125 Published in The Journal of Prevention of Alzheimer’s Disease (JPAD)
Published results from this study demonstrate that biomarkers of Alzheimer’s disease pathology (P-tau, total tau and Aβ42), neurodegeneration (NfL and neurogranin) and neuroinflammation (YKL-40, IL-6, IL-1β and TNFα) improved significantly after 28 days of treatment with PTI-125. Biomarker reductions were at least p< 0.001 by paired t-test. Biomarkers effects were seen in all patients in both cerebrospinal fluid (CSF) and plasma. PTI-125 was safe and well tolerated, with no observable drug-related adverse events.
Key results published from the Phase 2a study include:
- Total tau (T-tau) decreased 20% (p<0.001)
- Phosphorylated tau (P-tau) decreased 34% (p<0.0001)
- Neurofilament light chain (NfL), a marker for neurodegeneration, decreased 22% (p<0.0001)
- Neurogranin, a marker for cognitive decline, decreased 32% (p<0.0001)
- Neuroinflammatory marker YKL-40, an indicator of microglial activation, decreased 9% (p<0.0001)
- Proinflammatory Interleukin 6 (IL-6) decreased 14% (p<0.0001)
- Proinflammatory Interleukin 1 beta (IL-1β) decreased 11% (p<0.0001)
- Proinflammatory Tumor Necrosis Factor alpha (TNFα) decreased 5% (p<0.001)
- The ratio of CSF P-tau to Aβ42, a widely accepted biochemical value of Alzheimer’s disease, improved in all patients (p<0.001)
Although cognition and function were not assessed in this small Phase 2a study, independent research has shown that high levels of CSF biomarkers of P-tau and total tau/Aβ42 ratio correlate with worse performance on a wide range of memory and attention tests. Conversely, lowering biomarkers of disease may benefit patients.
“We are now conducting a confirmatory Phase 2b study of PTI-125 in Alzheimer’s disease,” said
Results of On-going Phase 2b Study Expected mid-2020
Sixty-four (64) patients with mild-to-moderate Alzheimer’s disease are enrolled in a randomized, placebo-controlled, confirmatory Phase 2b study to assess the safety, tolerability and biomarkers effects of PTI-125. More information for this study is available on-line at ClinicalTrials.gov:
https://clinicaltrials.gov/ct2/show/NCT04079803
About the Published Phase 2a Study
Phase 2a was a first-in-patient, open-label, multi-center, safety, pharmacokinetic and biomarker study of PTI-125 in the U.S. Thirteen patients with mild-to-moderate Alzheimer’s disease, age 50-85, received 100 mg oral PTI-125 twice daily for 28 days. A diagnosis of Alzheimer’s disease was confirmed with Mini-Mental State Examination (MMSE) ≥ 16 and ≤ 24 and a CSF T-tau/Aβ42 ratio ≥ 0.30. Safety was assessed by ECGs, clinical labs, adverse event monitoring and physical examinations. CSF was drawn from patients before dosing started and again after 28 continuous days of dosing with PTI-125. CSF samples were then analyzed for biomarkers of Alzheimer’s pathology (T-tau, P-tau, Aβ42); neurodegeneration (NfL, neurogranin); and neuroinflammation (YKL-40, IL-6, IL-1β and TNFα). A consulting biostatistician conducted an independent analysis of the data set.
Reference
“PTI-125 Reduces Biomarkers of Alzheimer’s Disease In Patients”,
The publication is available on-line: http://link.springer.com/article/10.14283/jpad.2020.6
About PTI-125
The target of PTI-125 is an altered form of filamin A (FLNA), a scaffolding protein. Altered FLNA in the brain disrupts the normal function of neurons, leading to Alzheimer’s pathology, neurodegeneration and neuroinflammation. Lead drug candidate PTI-125 is a proprietary small molecule that restores the normal shape and function of FLNA in the brain. This action improves the function of certain receptors in the brain, slows neurodegeneration and exerts powerful anti-neuroinflammatory effects. The underlying science for PTI-125 is published in peer-reviewed scientific journals, including
About Alzheimer's Disease
Alzheimer’s disease is a progressive brain disorder that destroys memory and thinking skills. Currently, there are no drug therapies to halt Alzheimer’s disease, much less reverse its course. In the U.S. alone, approximately 5.8 million people are currently living with Alzheimer’s disease, and approximately 487,000 people age 65 or older developed Alzheimer’s in 2019.5 The number of people living with Alzheimer’s disease is expected to grow dramatically in the years ahead, which may also result in a growing social and economic burden.6
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5, 6 Source: Alzheimer’s Association. 2019 Alzheimer’s Disease Facts and Figures. Available online at: https://www.alz.org/media/documents/alzheimers-facts-and-figures-2019-r.pdf
Source: Cassava Sciences, Inc.